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Abstract Cardiac myxoma (CM) is the most common benign cardiac tumor, and most CMs are left atrial myxomas (LAMs). Six variations of KIF1C, c.899 A > T, c.772 T > G, c.352 A > T, c.2895 C > T, c.3049 G > A, and c.*442_*443dup in left atrial myxoma tissues are identified by whole-exome sequencing (WES) and Sanger sequencing. RNA-seq and function experiments show the reduction of the expression of KIF1C and PRKAR1A caused by rare variations of KIF1C. KIF1C is observed to be located in the nucleus, bind to the promoter region of PRKAR1A, and regulate its transcription. Reduction of KIF1C decreases PRKAR1A expression and activates the PKA, which causes an increase in ERK1/2 phosphorylation and SRC-mediated STAT3 activation, a reduction of CDH1, TP53, CDKN1A, and BAX, and eventually promotes tumor formation both in vitro and in vivo. The results suggest that inhibition of KIF1C promotes the pathogenesis of LAM through positive feedback formed by the crosstalk between KIF1C and PRKAR1A.

Combining synthetic polymers and biomacromolecules prevents the occurrence of thrombogenicity and intimal hyperplasia in small-diameter vascular grafts (SDVGs). In the present study, an electrospinning poly (L)-lactic acid (PLLA) bilayered scaffold is developed to prevent thrombosis after implantation by promoting the capture and differentiation of endothelial colony-forming cells (ECFCs). The scaffold consists of an outer PLLA scaffold and an inner porous PLLA biomimetic membrane combined with heparin (Hep), peptide Gly-Gly-Gly-Arg-Glu-Asp-Val (GGG-REDV), and vascular endothelial growth factor (VEGF). Attenuated total reflection Fourier transform infrared (ATR-FTIR) spectroscopy, X-ray photoelectron spectroscopy (XPS), and contact angle goniometry were performed to determine successful synthesis. The tensile strength of the outer layer was obtained using the recorded stress/strain curves, and hemocompatibility was evaluated using the blood clotting test. The proliferation, function, and differentiation properties of ECFCs were measured on various surfaces. Scanning electronic microscopy (SEM) was used to observe the morphology of ECFCs on the surface. The outer layer of scaffolds exhibited a similar strain and stress performance as the human saphenous vein via the tensile experiment. The contact angle decreased continuously until it reached 56° after REDV/VEGF modification, and SEM images of platelet adhesion showed a better hemocompatibility surface after modification. The ECFCs were captured using the REDV + VEGF + surface successfully under flow conditions. The expression of mature ECs was constantly increased with the culture of ECFCs on REDV + VEGF + surfaces. SEM images showed that the ECFCs captured by the REDV + VEGF + surface formed capillary-like structures after 4 weeks of culture. The SDVGs modified by REDV combined with VEGF promoted ECFC capture and rapid differentiation into ECs, forming capillary-like structures in vitro. The bilayered SDVGs could be used as vascular devices that achieved a high patency rate and rapid re-endothelialization.

Autonomous vehicles are the most advanced intelligent vehicles and will play an important role in reducing traffic accidents, saving energy and reducing emission. Motion control for trajectory tracking is one of the core issues in the field of autonomous vehicle research. According to the characteristics of strong nonlinearity, uncertainty and chang-ing longitudinal velocity for autonomous vehicles at high speed steering condition, the robust trajectory tracking control is studied. Firstly, the vehicle system models are established and the novel target longitudinal velocity planning is carried out. This velocity planning method can not only ensure that the autonomous vehicle operates in a strong nonlinear coupling state in bend, but also easy to be constructed. Then, taking the lateral location deviation minimiz-ing to zero as the lateral control objective, a robust active disturbance rejection control path tracking controller is designed along with an extended state observer which can deal with the varying velocity and uncertain lateral dis-turbance effectively. Additionally, the feedforward-feedback control method is adopted to control the total tire torque, which is distributed according to the steering characteristics of the vehicle for additional yaw moment to enhance vehicle handing stability. Finally, the robustness of the proposed controller is evaluated under velocity-varying condi-tion and sudden lateral disturbance. The single-lane change maneuver and double-lane change maneuver under vary longitudinal velocity and different road adhesions are both simulated. The simulation results based on Matlab/Simulink show that the proposed controller can accurately observe the external disturbances and have good performance in trajectory tracking and handing stability. The maximum lateral error reduces by 0.18 meters compared with a vehicle that controlled by a feedback-feedforward path tracking controller in the single-lane change maneuver. The lateral deviation is still very small even in the double lane change case of abrupt curvature. It should be noted that our proposed control algorithm is simple and robust, thus provide great potential for engineering application.

Abstract Familial hypercholesterolemia (FH) is a severe inherited lipid metabolism dysfunction, characterized by high low‐density lipoprotein (LDL) cholesterol levels, mostly due to mutations in the LDL receptor (LDLR) gene. Whole exome sequencing was performed on a consanguineous Chinese FH family and identified a novel homozygous pathogenic mutation LDLR c.C2164T (p. Q722*), forming a novel truncated soluble LDLRQ722*. LDLRQ722* was secreted via the small extracellular vesicles (sEV) and located on the surface of sEV. LDLRQ722*exhibit ∼6% of the wild‐type LDLR activity. sEV containing LDLRQ722* protein reconstructed the lipid metabolism via heparan sulfate proteoglycans (HSPG) and clathrin‐mediated endocytosis. Currently, statins and PCSK9 inhibitors therapy are the mainstay treatment for FH. However, statins and PCSK9 inhibitors substantially vary depending on the residual LDLR activity, while LDLRQ722* reduced circulating LDL‐C levels independently of LDLR residual activity. The study provided new insight into the treatments of FH.

Aiming at the problems of model uncertainty, external interference of road conditions, and inherent nonlinearity of lateral movement of autonomous driving vehicles, this paper proposes an effective control technology for an automatic steering system, namely, the receding horizon $H_{\infty }$ control, which has good path tracking performance and can overcome external interference. First, a two-degree-of-freedom vehicle model and a road model are established. Then, the Hamilton equation is established using Pontriagin’s minimum principle, and the optimal control solution and the most serious disturbance are solved based on the minimax principle. Finally, in order to evaluate the receding horizon $H_{\infty }$ autonomous steering control method, lane change simulation and hardware in the loop simulation are developed to describe the effect of receding horizon $H_{\mathrm {\infty }}$ . The simulation results show that the model predictive control (MPC) and linear matrix inequality (LMI) controller will exhibit oscillation and instability under the condition of external interference. To improve the stability, the $H_{\infty }$ controller reduces part of the performance, while the rolling horizon $H_{\mathrm {\infty }}$ strategy can ensure the robustness of automatic steering and has a certain anti-interference performance.

The nonlinear vibration effect of nanobeam and problem of the pull-in between the nanobeam and driven plate are the factors which prevent nano-resonator from improving the performance. The nonlinear governing differential equation is built by considering the axial force with piezoelectric controller. The piezoelectric time-delay electrostatic pull-in control is studied and the first-order approximate solution of nonlinear equation is gotten by using the method of multi-scale. The amplitude–frequency and phase frequency response equation of nonlinear vibration system are given for the primary resonance response of the nanobeam. The relationship between the control effect and feedback control parameters is studied. It is found that the piezoelectric time-delay control can change the critical voltage but not the critical position. The axial force can affect the performance of nanobeam.

Aortic dissection (AD) is a life-threatening disease with high morbidity and mortality, and effective pharmacotherapeutic remedies for it are lacking. Therefore, AD’s molecular pathogenesis and etiology must be elucidated. The aim of this study was to investigate the possible mechanism of mediator complex subunit 12 (human: MED12, mouse: Med12)involvement in AD. Firstly, we examined the expression of MED12 protein (human: MED12, mouse: Med12) in the aortic tissues of AD patients and AD mice. Subsequently, Med12 gene silencing was accomplished with RNA interference (siRNA). The effects of Med12 on AD and the possible biological mechanisms were investigated based on the proliferation, senescence, phenotypic transformation, and its involved signal pathway of mouse aortic smooth muscle cells (MOVAS), s. The results show that the expression of MED12 in the aortae of AD patients and AD mice was decreased. Moreover, the downregulation of Med12 inhibited the proliferation of MOVAS and promoted senescence. Further research found that Med12, as an inhibitor of the TGFβ1 signaling pathway, reduced the expression of Med12 and enhanced the activity of the TGFβ1 nonclassical signaling pathway, while TGFβ1 inhibited the phenotype transformation and proliferation of MOVAS by inhibiting Med12 synthesis. In conclusion, Med12 affected the phenotype, proliferation, and senescence of MOVAS through the TGFβ signaling pathway. This study provides a potential new target for the prevention and treatment of AD.

Background/Aims: Diabetes mellitus (DM) has been demonstrated to have a strong association with heart failure. Conventional echocardiographic analysis cannot sensitively monitor cardiac dysfunction in type I diabetic Akita hearts, but the phenotype of heart failure is observed in molecular levels during the early stages. Methods: Male Akita (Ins2WT/C96Y) mice were monitored with echocardiographic imaging at various ages, and then with conventional echocardiographic analysis and speckle-tracking based strain analyses. Results: With speckle-tracking based strain analyses, diabetic Akita mice showed changes in average global radial strain at the age of 12 weeks, as well as decreased longitudinal strain. These changes occurred in the early stage and remained throughout the progression of diabetic cardiomyopathy in Akita mice. Speckle-tracking showed that the detailed and precise changes of cardiac deformation in the progression of diabetic cardiomyopathy in the genetic type I diabetic Akita mice were uncoupled. Conclusions: We monitored early-stage changes in the heart of diabetic Akita mice. We utilize this technique to elucidate the underlying mechanism for heart failure in Akita genetic type I diabetic mice. It will further advance the assessment of cardiac abnormalities, as well as the discovery of new drug treatments using Akita genetic type I diabetic mice.

BackgroundIdiopathic ventricular tachycardia (VT) is a type of cardiac arrhythmia occurring in structurally normal hearts. The heritability of idiopathic VT remains to be clarified, and numerous genetic factors responsible for development of idiopathic VT are as yet unclear. Variations in FGF12 (fibroblast growth factor 12), which is expressed in the human ventricle and modulates the cardiac Na+ channel NaV1.5, may play an important role in the genetic pathogenesis of VT. Methods and ResultsWe tested the hypothesis that genetic variations in FGF12 are associated with VT in 2 independent Chinese cohorts and resequenced all the exons and exon–intron boundaries and the 5′ and 3′ untranslated regions of FGF12 in 320 unrelated participants with idiopathic VT. For population‐based case–control association studies, we chose 3 single‐nucleotide polymorphisms—rs1460922, rs4687326, and rs2686464—which included all the exons of FGF12. The results showed that the single‐nucleotide polymorphism rs1460922 in FGF12 was significantly associated with VT after adjusting for covariates of sex and age in 2 independent Chinese populations: adjusted P=0.015 (odds ratio: 1.54 [95% CI, 1.09–2.19]) in the discovery sample, adjusted P=0.018 (odds ratio: 1.64 [95% CI, 1.09–2.48]) in the replication sample, and adjusted P=2.52E‐04 (odds ratio: 1.59 [95% CI, 1.24–2.03]) in the combined sample. After resequencing all amino acid coding regions and untranslated regions of FGF12, 5 rare variations were identified. The result of western blotting revealed that a de novo functional variation, p.P211Q (1.84% of 163 patients with right ventricular outflow tract VT), could downregulate FGF12 expression significantly. ConclusionsIn this study, we observed that rs1460922 of FGF12 was significantly associated with VT and identified that a de novo variation of FGF12 may be an important genetic risk factor for the pathogenesis of VT.

Information-centric networking (ICN) technology matches many major requirements of vehicular ad hoc networks (VANETs) in terms of its connectionless networking paradigm accordant with the dynamic environments of VANETs and is increasingly being applied to VANETs. However, wireless transmissions of packets in VANETs using ICN mechanisms can lead to broadcast storms and channel contention, severely affecting the performance of data dissemination. At the same time, frequent changes of topology due to driving at high speeds and environmental obstacles can also lead to link interruptions when too few vehicles are involved in data forwarding. Hence, balancing the number of forwarding vehicular nodes and the number of copies of packets that are forwarded is essential for improving the performance of data dissemination in information-centric networking for vehicular ad-hoc networks. In this paper, we propose a context-aware packet-forwarding mechanism for ICN-based VANETs. The relative geographical position of vehicles, the density and relative distribution of vehicles, and the priority of content are considered during the packet forwarding. Simulation results show that the proposed mechanism can improve the performance of data dissemination in ICN-based VANET in terms of a successful data delivery ratio, packet loss rate, bandwidth usage, data response time, and traversed hops.

Independent gear-shifting actuation systems, which are based on linear electromagnetic actuators (LEMAs), have tremendous potential to minimize the shifting duration of automated mechanical transmission (AMT). A velocity estimator based on the measurements of current is designed to achieve sensorless control of the actuator by using only electrical subsystem, thus avoiding the use of a complete system model that contains mechanical uncertainties. The elimination of the position sensor simplifies the structure of the gear-shifting system and reduces the manufacturing cost. To enhance the robustness of the position control, model-assisted reduced-order extended state observer (ESO) based cascade controller is constructed, which take parameter uncertainties and external load force as the lumped disturbance to observe and compensate them dynamically. Finally, simulation and experimental results are shown to demonstrate the effectiveness of the proposed velocity estimator and control method.

At present, there are few studies on bearing characteristics and settlement laws of composite foundations in collapsible loess areas. Taking long and short pile-net composite foundations (CFG pile refers to Cement Fly Ash Gravel long pile and CSC pile refers to Cement-Soil Compacted short pile) in collapsible loess area of Yinxi high-speed railway as the research object, three-dimensional numerical simulation is carried out on long and short pile composite foundations by finite element method. Then, mechanical characteristics and settlement laws of long and short pile-net composite foundations are studied. The conclusions are as follows: under the loading of the embankment, the CFG pile mainly bears most of the load; at the same height within the embankment, especially near the centerline of the embankment, the vertical pressure at the pile top is greater than that of the soil between the piles, and the vertical stress difference between the pile top and the soil between the piles along the embankment slope direction (namely, away from the embankment centerline) gradually decreases; the maximum lateral displacement of the composite foundation occurs at the embankment slope; the settlement deformation and vertical displacement of the overall foundation, the soil between the piles and the pile body are gradually reduced from the embankment centerline to the embankment slope; the settlement deformation of the CFG pile is relatively smaller. The results of numerical simulation analysis are basically consistent with those of the test section. This paper is a research based on a real engineering project and can provide some critical references for the design and construction of other similar engineering cases in the future. [ABSTRACT FROM AUTHOR]

To intuitively analyze and diagnose why high railway traffic often occurs, this paper builds a Bayesian network on a rail transit system, for instance, the Shanghai Metro L1, to explore it from different angles such as holidays, mega-events, bad weather and sudden accidents. The fuzzy set theory is also integrated to quantify the conditional probability of some events using the fuzzy languages. It turns out that the Bayesian network constructed can well infer the probability of massive passenger traffic, and diagnose the dominant factors that may cause it. Hereby, the rail transit management authorities can take proper measures against it to reduce the risks the high rail traffic may impose. [ABSTRACT FROM AUTHOR]

The geology along the Yinxi High-speed Railway (YXZQ-5 subgrade on the Gansu-Ningxia section) is complex, with a large number of special geotechnical conditions and other unfavorable geological conditions. The hydrogeology, freezing depth, and seismic intensity along the line are different. In addition, the railway has a high design speed and high requirements for anti-deformation of the subgrade. In this paper, based on the subgrade treatment project of the Gansu-Ningxia section of the Yinxi Railway, the indoor compressive strength test of cementimproved soil and the field test of cement-improved soil were conducted. The cement mix ratios of the embankment at the bottom of the foundation bed, the embankment below the foundation bed, and the improved cushion were determined, respectively. The relationship between the optimal moisture content of the filler and the maximum dry density and the relationship between the optimal moisture content of the filler and the compaction coefficient were determined, respectively. The relationship between the ash content and the strength of cement-improved soil and the optimal moisture content of cement-improved soil were obtained. The results show that the cement-improved soil reinforcement method can better improve the strength of collapsible loess. [ABSTRACT FROM AUTHOR]

Background and Purpose: ANRIL has long been considered as the strongest candidate gene at the 9p21 locus, robustly associated with stroke and coronary artery disease. However, the underlying molecular mechanism remains unknown. The present study works to elucidate such a mechanism., Methods: Using expression quantitative loci analysis, we identified potential genes whose expression may be influenced by genetic variation in ANRIL. To verify the identified gene(s), knockdown and overexpression of ANRIL were evaluated in human umbilical vein endothelial cells and HepG2 cells. Ischemic stroke and coronary artery disease risk were then evaluated in the gene(s) demonstrated to be mediated by ANRIL in 3 populations of Chinese Han ancestry: 2 ischemic stroke populations consisting of the Central China cohort (903 cases and 873 controls) and the Northern China cohort (816 cases and 879 controls) and 1 coronary artery disease cohort consisting of 772 patients and 873 controls., Results: Expression quantitative loci analysis identified CARD8 among others, with knockdown of ANRIL expression decreasing CARD8 expression and overexpression of ANRIL increasing CARD8 expression. The minor T allele of a previously identified CARD8 variant (rs2043211) was found to be significantly associated with a protective effect of ischemic stroke under the recessive model in 2 independent stroke cohorts. No significant association was found between rs2043211 and coronary artery disease., Conclusions: CARD8 is a downstream target gene regulated by ANRIL. Single nucleotide polymorphism rs2043211 in CARD8 is significantly associated with ischemic stroke. ANRIL may increase the risk of ischemic stroke through regulation of the CARD8 pathway.